The prevalence of drug abuse in today's society demands that the scientific community be informed on may aspects of compounds subject to illicit use. Over the last ten years there has been a steady increase in the abuse of a new synthetic compound, phencyclidine (PCP). This CNS active drug is unique in that it possesses local anesthetic, sedative-hypnotic, psychomotor stimulant, and hallucinogenic properties. Little is known of the neurochemical mechanisms through which these effects are produced. We propose to study the neurochemical pharmacology of PCP in the rat CNS in order to identify those neurochemical processes which are effected by PCP. We will examine the effects of both acute and chronic administration of PCP on several aspects of neurotransmitter biochemistry. Our primary focus will be on the biogenic amines, but we will also examine certain aspects of the cholinergic and GABA-ergic systems in the rat brain. The endogenous concentration of each neurotransmitter (and some of their precursors and metabolites) will be determined in seven brain areas using both fluorometric and radioenzymatic techniqes. Synthesis and turnover rates of the biogenic amines will be subcellular distribution of PCP in the brain at several time intervals following administration. The dose-response and temporal characteristics of observed effects will be related and integrated into a working hypothesis concerned with delineating the neurochemical mechanism(s) and site(s) of action of PCP.